Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion
M J Leandro, J C W Edwards, G Cambridge, M J Leandro, J C W Edwards, G Cambridge
Abstract
Objectives: To obtain evidence for dose response and to extend evidence of safety and efficacy for B lymphocyte depletion in rheumatoid arthritis.
Methods: Twenty two patients with rheumatoid arthritis received a total of 29 treatments with five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or high dose prednisolone (PR) on an open basis as follows; cohort I: RTX 1400 mg/m(2), CP 750x2+PR; cohort II: RTX 300-700 mg/m(2), -CP+/-PR); cohort III: RTX 600-700 mg/m(2), CP 750x2+PR; cohort IV: RTX 1200 mg/m(2), CP 750x2-PR; cohort V: RTX 500 mg/m(2), CP 750x2+PR. American College of Rheumatology (ACR) criteria of improvement at six months were chosen as the primary outcome measure. Disease activity scores and total duration of improvement and of B cytopenia were also recorded.
Results: No major adverse events attributable to treatment were seen. ACR grades of improvement at six months were as follows: cohort I: ACR70x3, ACR50x2; cohort II: ACR20x1, ACR0x3; cohort III: ACR70x6, ACR50x2, ACR20x2; cohort IV: ACR70x2, ACR50x2, ACR20x1, ACR0x1; cohort V: ACR0x4.
Conclusions: B lymphocyte depletion in rheumatoid arthritis has so far proved to be safe and associated with major improvement with protocols including RTX 600 mg/m(2) or more and CP, but not with more limited protocols. These observations provide an initial basis for the design of formal trials of B cell depletion and other B cell directed treatments, including a phase II controlled trial now in progress.
Figures
References
- J Lab Clin Med. 1999 Nov;134(5):445-50
- Immunology. 1998 May;94(1):56-63
- Semin Oncol. 1999 Oct;26(5 Suppl 14):88-96
- Arthritis Rheum. 2000 Mar;43(3):608-16
- Rheumatology (Oxford). 2001 Feb;40(2):205-11
- N Engl J Med. 1978 Apr 20;298(16):869-71
- Lancet. 1981 Oct 17;2(8251):839-42
- Rheumatol Int. 1983;3(4):183-6
- Clin Rheum Dis. 1985 Dec;11(3):551-72
- Arthritis Rheum. 1988 Mar;31(3):315-24
- J Exp Med. 1991 Feb 1;173(2):487-9
- Immunol Today. 1993 May;14(5):215-21
- Blood. 1994 Jan 15;83(2):435-45
- Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8562-6
- Arthritis Rheum. 1995 Jun;38(6):727-35
- Annu Rev Immunol. 1995;13:127-49
- APMIS. 1997 Apr;105(4):257-63
- J Clin Oncol. 1997 Oct;15(10):3266-74
- Arthritis Rheum. 1998 Aug;41(8):1481-8
Source: PubMed